Metabonomics and Toxicology

Zhao, Liang; Hartung, Thomas

doi:10.1007/978-1-4939-2377-9_15

Cited by 13 publications

(8 citation statements)

References 76 publications

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“…MS-based metabolomics allows targeted and untargeted metabolome analysis and it has become an indispensable tool in metabolome analysis (Milne et al, 2013 ); moreover, MS has a broader dynamic range, exhibits a high sensitivity and selectivity (Zhao and Hartung, 2015 ), and allows determining metabolite fingerprints for establishing metabolome libraries, which facilitate the identification of metabolites (Martins-de-Souza, 2014 ).…”

Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

“…Finally, MS-based metabolomic techniques offer high selectivity and sensitivity for metabolites' identification and quantification. In fact, they are considered as the most appropriate techniques for the detection of large numbers of metabolites, and, in combination with advanced and high-throughput platforms, they may help decrease the complexity of metabolite separation (Zheng et al, 2011 ; Zhao and Hartung, 2015 ). In particular, for the total screening of the small molecules in a biological system, MS non-targeted metabolomics is a powerful tool for the identification of metabolite signals present in spectra (Naz et al, 2014 ).…”

Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

“…However, it is a relatively insensitive technique, and can only detect metabolites in high concentrations. The annotation is restricted to a limited number of low molecular weight molecules, and this is the major pitfall of this application (Jansson et al, 2009 ; Zhao and Hartung, 2015 ). Indeed, sensitivity depends on the natural concentration of the atoms in the matrix and, to improve sensitivity, long times of analysis, higher magnetic fields, and cryogenic probes are needed (Keun et al, 2002 ).…”

Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

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Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

2016

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The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

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Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

Section: Volatile and Non-volatile Compounds: Detection Methods And Dmentioning

confidence: 99%

See 1 more Smart Citation

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

2016

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“…In contrast, MS has a broader dynamic range and exhibits a better sensitivity and selectivity. In the past few years, the use of MS in metabolomics is rapidly growing [31] . A combination of 1 H-NMR and MS technologies would result in a better coverage of the complete metabolome.…”

Section: Metabolomics: Analytical Strategiesmentioning

confidence: 99%

Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease

Preter¹

2015

Dig Dis

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Background: Crohn's disease and ulcerative colitis represent the 2 major phenotypes of inflammatory bowel disease (IBD) that are characterized by chronic inflammation of all or parts of the gastrointestinal tract. The pathogenesis of both diseases is influenced by genetic predispositions as well as microbial and environmental factors. Currently, there is an emerging consensus hypothesis that a microbial dysbiosis is involved in initiating the disease or in maintaining it. These compositional alterations may be reflected in altered metabolic activities of the gut microbiota and has led to the use of ‘omic' profiling to improve the understanding of the pathophysiology of IBD. Key Messages: In the past few years, a metabolic approach has increasingly been applied in a number of studies of experimental and human IBD which were mostly focused on exploring disease-related metabolites to gain more insight into metabolic pathways. Metabolomics involves the high throughput identification, characterization and quantification of small molecule metabolites by different analytical techniques and has been performed in different biofluids such as serum/plasma, urine or fecal samples. The application of such a metabolite profiling technique has revealed different metabolites that allow the discrimination of IBD patients from healthy controls. In addition, separate IBD subtypes could be differentiated. Some of these metabolic changes were directly associated to alterations of specific gut microbial populations, implying a perturbation in the gut microbiome in the development of IBD. Conclusions: This review covers the emerging contribution of metabolomics for the discovery of an IBD signature and to identify biomarkers linked with a metabolic imbalance. For the implementation of metabolomics as a diagnostic tool in IBD, large prospective cohort studies are necessary.

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“…The National Research Council Report “Toxicity Testing in the 21st Century: a Vision and a Strategy (2007)” ( NRC 2007 ) promoted the use of nonanimal models and called for embracing new technologies and basing assessments on toxicological mechanisms related to human biology and exposure. The proposed suite of tools includes the combination of computational models (integrative and targeted quantitative structure–activity predictions) and multiple in vitro assays, pathway-based approaches and toxicokinetic modeling ( Browne et al 2015 ; Bisson 2012 ; Zhao and Hartung 2015 ; Perkins et al 2014 ; Kleinstreuer et al 2014 ; Tice et al 2013 ; Kavlock et al 2012 ).…”

Section: Methodsmentioning

confidence: 99%

Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations

Miller

Goodson

Manjili

et al. 2017

Environ Health Perspect

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Background:The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis.Objective:Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August 2015 evaluated the scientific support for the low-dose mixture hypothesis of carcinogenesis and developed a research agenda. Here we describe the science that supports this novel theory, identify knowledge gaps, recommend future methodologies, and explore preventative risk assessment and policy decision-making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology.Discussionand Conclusions: The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in predicting human responses; evaluate biological events leading to carcinogenesis both spatially and temporally; examine the overlap between measurable cancer hallmarks and characteristics of carcinogens; incorporate epigenetic biomarkers, in silico modelling, high-performance computing and high-resolution imaging, microbiome, metabolomics, and transcriptomics into future research efforts; and build molecular annotations of network perturbations. The restructuring of many existing regulatory frameworks will require adequate testing of relevant environmental mixtures to build a critical mass of evidence on which to base policy decisions.Citation:Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. 2017. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125:163–169; http://dx.doi.org/10.1289/EHP411

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Metabonomics and Toxicology

Cited by 13 publications

References 76 publications

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease

Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations

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